Understanding viral-host interactions at the organismal, cellular, and molecular levels are vital in mitigating viral pathogenesis. The goals of this project are to discover the viral microbiome and the role of innate immunity in the regulation of viral symbioses in the model organism Hydra. By doing so, it will be determined whether Hydra contain viruses similar to human viruses as well as testing Hydra-specific genes responsive to viral presence. Hydra provide an ideal model to test these host-pathogen interactions because of their simplistic composition, their ease of experimental manipulation, and their epithelial exposure to the environment without a protective barrier. Further, Hydra lack adaptive immunity features, do not contain motile phagocytic cells, and only utilize mucus as a means to preserve its epithelium. Therefore, Hydra are uniquely suited for the study of host-pathogen interactions at the mucosal epithelium. To establish this, the project consists of two specific aims: 1.) Identify Hydra viral communities utilizing viral metagenomics. The purpose of this aim is to discover the viruses associating with Hydra, whether they are induced under stress, and to deduce whether these viruses are involved in human pathogenesis. 2.) Elucidate the Hydra antiviral response in the presence of cytosolic nucleic acids. Specific Hydra antiviral innate immune response genes possess greater similarities to humans than that of flies and worms. Therefore, monitoring Hydra innate immune genes in response to viral presence will clarify the effects made by viruses at the epithelium. By accomplishing these two aims, viruses that cause pathogenic conditions in Hydra will be identified as well as viruses that similarly cause human pathogenesis harbored within Hydra. Once identified, cultivatable viruses can then be tested in this Hydra innate immunity model system. If the etiologic agent cannot be cultured, the identified agent genes will be used to test Hydra antiviral recognition. Further, by identifying the Hydra antiviral genes responsive to viral infection, Hydra will be manipulated through gene knockdown, to determine which genes are vital in either limiting viral pathogenesis or promoting viral symbiosis.